The delivery of drugs by aerosolization to neonates and infants who are breathing on a ventilator (mechanically ventilated) has been problematic and unsuccessful. The inherent properties of the ventilator and the nebulizer have contributed to the inefficacious drug delivery. Nebulizers are devices which create aerosolized particles for inhalation. These particles are usually composed of water droplets containing dissolved drugs. However, the particles may be lipid or other types of liquid droplets or dry.
Inhalation is considered the best method for drug delivery to the lung and possibly the heart. Drugs delivered by inhalation are targeted directly to the lung, permitting much lower doses for effect in the lung than if given systemically. Inhalation is the natural route to the lung, permitting homogeneous distribution of drugs in the lung with an even application of dose. Despite a general agreement that inhalation is the best route of drug administration, attempts to administer aerosol drugs to mechanically ventilated or spontaneously breathing infants have been unsuccessful. Even efforts to produce aerosols for inhalation by children and adults have not met with great success. Less than 2% of drugs put in nebulizers deposit in the lungs of mechanically ventilated or spontaneously breathing infants. A range between 5% and 20% of drugs in the nebulizers reach the lungs of children or adults.
Nebulizers of various designs are used for administering drugs. One type of nebulizer that is widely used is an ultrasonic nebulizer. A vibrating crystal in the bottom of a vessel that contains the drug in solution can produce an aerosol of droplets about 1 to 5 microns in diameter contained in a chamber (cap) above the liquid. Ultrasonic nebulizers can be used with a mouthpiece for inhalation by natural breathing or can be connected to a ventilator for administration through an endotracheal tube. In the case of inhalation, a portion of the inhaled aerosol is exhaled from the lungs, rather than being deposited on the surfaces of the lungs. In mechanically ventilated infants, a large fraction of the drug is also lost upon expiration and by adhesion to the cap and deposition on the surfaces of the hoses of the ventilator and the endotracheal tube.
Infant ventilators are continuous flow ventilators. This means that air or oxygen continually flows through the ventilator when the exhalation valve is open. If the number of breaths per minute is set at 30 and the inspiration time is set at 0.5 sec. (common ventilator settings for infants) the expiration time is 1.5 seconds. During this 1.5 seconds gas flows through the ventilator continuously. If the nebulizer is positioned directly in line with the ventilator tubing (in. series), gas will blow through the nebulizer, wasting the aerosolized drug that flows through the ventilator tube and out though the outlet valve of the ventilator during expiration and rest.